Abstract 1674: The NQO1 C609T polymorphism is associated with poorer response to AC adjuvant therapy in the treatment of breast cancer

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC A non-synonymous SNP in the NAD(P)H: Quinone Oxidoreductase 1 gene has previously been implicated in the response of breast cancer patients to anthracycline containing regimens in a retrospective cohort study. NQO2 is 54% homologous to NQO1 at the primary protein structure and, despite the lack of a characterised endogenous electron donating cofactor for NQO2, the two enzymes share numerous substrates. NQO2, in contrast to NQO1, is additionally capable of reducing reactive quinone metabolites of estradiol. The NQO2 gene has a non-synonymous SNP that has previously been shown to result in a lower average NQO2 activity in cohorts of bladder and ovarian cancer patients. It is unknown if the NQO2 SNP impacts on survival in breast cancer. Genomic DNA samples from 239 women with early breast cancer were genotyped for the NQO1 (rs1800566) and NQO2 (rs1143684) SNPs. All of the participants were recruited from Medical Oncology out-patient clinics within the Newcastle upon Tyne Hospitals NHS Foundation Trust and were treated with an AC adjuvant therapy regimen with curative intent. Median follow up was 78 months and followed a standard protocol. Genotyping was done by the Taqman RT-PCR method. The NQO1 SNP was associated with a decreased time to progression (HR 2.8, 95%CI 1.4-5.64, p=0.003), decreased overall survival (HR 3.6, 95%CI 1.4-10, p=0.007) and a lower likelihood of having a dose delay, all indicative of NQO1 mediated sensitisation to the effects of doxorubicin. The NQO2 SNP had no impact on the cohort as a whole but was associated with a decreased overall survival (p=0.009, log-rank) and time to progression (p=0.004, log rank) in patients who were oestrogen receptor (ER) negative. This study confirms the previous observation of NQO1 genotype influencing response to anthracyclines and indicates a potential impact of an NQO2 SNP on the prognosis of ER negative breast cancer. The mechanism by which NQO2 genotype influences breast survival remains to be elucidated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1674.